Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transcriptional activator GLI3

Gene

Gli3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri480 – 505C2H2-type 1PROSITE-ProRule annotationAdd BLAST26
Zinc fingeri513 – 540C2H2-type 2PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri546 – 570C2H2-type 3PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri576 – 601C2H2-type 4PROSITE-ProRule annotationAdd BLAST26
Zinc fingeri607 – 632C2H2-type 5PROSITE-ProRule annotationAdd BLAST26

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-5610785 GLI3 is processed to GLI3R by the proteasome
R-MMU-5610787 Hedgehog 'off' state
R-MMU-5632684 Hedgehog 'on' state

Names & Taxonomyi

Protein namesi
Recommended name:
Transcriptional activator GLI3
Alternative name(s):
GLI3 form of 190 kDa
Short name:
GLI3-190
GLI3 full-length protein
Short name:
GLI3FL
Cleaved into the following chain:
Alternative name(s):
GLI3 C-terminally truncated form
GLI3 form of 83 kDa
Short name:
GLI3-83
Gene namesi
Name:Gli3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:95729 Gli3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cilium, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Several mutations result in developmental defects of cranofacial and limb structures. In particular the add (anterior digit-pattern deformity) and pdn (polydactyly Nagoya) alleles.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000472031 – 1583Transcriptional activator GLI3Add BLAST1583
ChainiPRO_00004061381 – ?Transcriptional repressor GLI3R

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei175Omega-N-methylarginineCombined sources1
Cross-linki438Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki462Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei664PhosphoserineBy similarity1
Cross-linki773Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki779Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Cross-linki779Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki784Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki800Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei849Phosphoserine; by PKABy similarity1
Modified residuei865Phosphoserine; by PKABy similarity1
Modified residuei877Phosphoserine; by PKABy similarity1
Modified residuei907Phosphoserine; by PKABy similarity1
Modified residuei980Phosphoserine; by PKABy similarity1
Modified residuei1006Phosphoserine; by PKABy similarity1

Post-translational modificationi

Phosphorylated by DYRK2 (in vitro) (By similarity). Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylation is essential for its proteolytic processing.By similarity1 Publication
Transcriptional repressor GLI3R, a C-terminally truncated form, is generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through proteolytic processing. This process requires PKA-primed phosphorylation of GLI3, ubiquitination of GLI3 and the presence of BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it to translocate into the nucleus, and repress Hh target genes. When Hh signaling is initiated, SUFU dissociates from GLI3FL and this has two consequences. First, GLI3R production is halted. Second, free GLI3FL translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Phosphorylated in vitro by ULK3.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ61602
PaxDbiQ61602
PRIDEiQ61602

PTM databases

iPTMnetiQ61602
PhosphoSitePlusiQ61602

Expressioni

Gene expression databases

BgeeiENSMUSG00000021318 Expressed in 315 organ(s), highest expression level in urinary bladder
CleanExiMM_GLI3
ExpressionAtlasiQ61602 baseline and differential
GenevisibleiQ61602 MM

Interactioni

Subunit structurei

The phosphorylated form interacts with BTRC (By similarity). The full-length GLI3 form (GLI3FL) interacts with SUFU and this interaction regulates the formation of either repressor or activator forms of GLI3. Its association with SUFU is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A. Interacts with KIF7. The activator form of GLI3 (GLI3A) but not the repressor form (GLI3R) can interact with TRPS1. Interacts with ZIC1. Interacts with ZIC3 (via C2H2-type domains 3, 4 and 5); the interaction enhances its transcriptional activity (By similarity). Interacts with WRD11; the interaction associates EMX1 with GLI3 (PubMed:29263200).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199944, 6 interactors
ComplexPortaliCPX-151 GLI3-SUFU complex
CORUMiQ61602
STRINGi10090.ENSMUSP00000106137

Structurei

3D structure databases

ProteinModelPortaliQ61602
SMRiQ61602
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi120 – 199Pro-richAdd BLAST80
Compositional biasi849 – 910Ser-richAdd BLAST62
Compositional biasi1494 – 1514Asp/Glu-rich (acidic)Add BLAST21

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri480 – 505C2H2-type 1PROSITE-ProRule annotationAdd BLAST26
Zinc fingeri513 – 540C2H2-type 2PROSITE-ProRule annotationAdd BLAST28
Zinc fingeri546 – 570C2H2-type 3PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri576 – 601C2H2-type 4PROSITE-ProRule annotationAdd BLAST26
Zinc fingeri607 – 632C2H2-type 5PROSITE-ProRule annotationAdd BLAST26

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00900000140802
HOGENOMiHOG000290688
HOVERGENiHBG005844
InParanoidiQ61602
KOiK06230
OMAiQYGNCLN
OrthoDBiEOG091G01XS
PhylomeDBiQ61602
TreeFamiTF350216

Family and domain databases

InterProiView protein in InterPro
IPR032851 GLI3
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PANTHERiPTHR19818:SF5 PTHR19818:SF5, 1 hit
PfamiView protein in Pfam
PF00096 zf-C2H2, 5 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 5 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 4 hits
PS50157 ZINC_FINGER_C2H2_2, 5 hits

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q61602-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEAQAHSSTA TERKKAENSI GKCPTRTDVS EKAVASSTTS NEDESPGQIY
60 70 80 90 100
HRERRNAITM QPQSVQGLNK ISEEPSTSSD ERASLIKKEI HGSLPHLAEP
110 120 130 140 150
SLPYRGTVFA MDPRNGYMEP HYHPPHLFPA FHPPVPIDAR HHEGRYHYDP
160 170 180 190 200
SPIPPLHVPS ALSSSPTYPD LPFIRISPHR NPTAASESPF SPPHPYINPY
210 220 230 240 250
MDYIRSLHSS PSLSMISAAR GLSPTDAPHA GVSPAEYYHQ MALLTGQRSP
260 270 280 290 300
YADILPSAAT AGAGAIHMEY LHAMDSTRFP SPRLSARPSR KRTLSISPLS
310 320 330 340 350
DHSFDLQTMI RTSPNSLVTI LNNSRSSSSA SGSYGHLSAS AISPALSFTY
360 370 380 390 400
PSAPVSLHMH QQILSRQQSL GSAFGHSPPL IHPAPTFPTQ RPIPGIPTVL
410 420 430 440 450
NPVQVSSGPS ESSQSKPTSE SAVSSTGDPM HNKRSKIKPD EDLPSPGSRG
460 470 480 490 500
QQEQPEGTTL VKEEADKDES KQEPEVIYET NCHWEGCTRE FDTQDQLVHH
510 520 530 540 550
INNDHIHGEK KEFVCRWLDC SREQKPFKAQ YMLVVHMRRH TGEKPHKCTF
560 570 580 590 600
EGCTKAYSRL ENLKTHLRSH TGEKPYVCEH EGCNKAFSNA SDRAKHQNRT
610 620 630 640 650
HSNEKPYVCK IPGCTKRYTD PSSLRKHVKT VHGPEAHVTK KQRGDMHPRP
660 670 680 690 700
PPPRDSGSHS QSRSPGRPTQ GAFGEQKELS NTTSKREECL QVKTVKAEKP
710 720 730 740 750
MTSQPSPGGQ SSCSSQQSPI SNYSNSGLEL PLTDGGSVAD LSAIDETPIM
760 770 780 790 800
DSTISTATTA LALQARRNPA GTKWMEHIKL ERLKQVNGMF PRLNPILPSK
810 820 830 840 850
APAVSPLIGN GTQSNNNYSS GGPGTLLPSR SDLSGVDFTV LNTLNRRDSN
860 870 880 890 900
TSTISSAYLS SRRSSGISPC FSSRRSSEAS QAEGRPQNVS VADSYDPIST
910 920 930 940 950
DASRRSSEAS QGDGLPSLLS LTPVQQYRLK AKYAAATGGP PPTPLPHMER
960 970 980 990 1000
LSLKTKMALL GEGRDSGVTL PPVHPPRRCS DGGGHTYRGR HLMPHDALAN
1010 1020 1030 1040 1050
SVRRASDPVR TVSENMSLAR VQRFSSLNSF NPPNLPPSVE KRSLVLQNYT
1060 1070 1080 1090 1100
RQESSQPRYF QASPCPPSIT ENVALEALTM DADANLNDED LLPDDVVQYL
1110 1120 1130 1140 1150
NSQNQTGYGQ QLQSGISEDS KVAHEPEDLD LAGLPDSHVG QEYPALEQPC
1160 1170 1180 1190 1200
SEGSKTDLPI QWNEVSSGTS DLSSSKLKCG QQRPSAQQPR GFGLYNNMVV
1210 1220 1230 1240 1250
HPHNLWKVGT GPAGGYQTLG ENSSTYNGPE HFAIHSGDGL GTNGNTFHEQ
1260 1270 1280 1290 1300
PFKTQQYGSQ LNRQPLTSSA LDHACGTGIQ GSKLKGNSLQ ENGGLLDFSL
1310 1320 1330 1340 1350
SVAPNELAGN TVNGMQTQDQ MGQGYIAHQL LSGSMQHQGP SRPGQQVLGQ
1360 1370 1380 1390 1400
VGATSHINIY QGTESCLPGT QDNSSQPSSM AAIRGYQPCA SYGGNRRQAM
1410 1420 1430 1440 1450
PRGNLTLQQG QLSDMSQSSR VNSIKMEAQG QSQQLCSTVQ NYSGQFYDQT
1460 1470 1480 1490 1500
MGFSQQDRKA GSFSLSDANC LLQGNGTENS ELLSPGANQV TSTVDSFESH
1510 1520 1530 1540 1550
DLEGVQIDFD AIIDDGDHTS LMSGALSPSI IQNLSHSSSR LTTPRASLPF
1560 1570 1580
PSLSMGTTNM AIGDMSSLLT SLAEESKFLA VMQ
Length:1,583
Mass (Da):171,655
Last modified:September 11, 2007 - v2
Checksum:i37ECC0C3ACF26C24
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q3UMJ8Q3UMJ8_MOUSE
Transcriptional activator GLI3
Gli3
596Annotation score:
A0A1Y7VKQ8A0A1Y7VKQ8_MOUSE
Transcriptional activator GLI3
Gli3
77Annotation score:

Sequence cautioni

The sequence CAA64543 differs from that shown. Reason: Frameshift at position 1552.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti209S → C in CAA64543 (PubMed:8688459).Curated1
Sequence conflicti428D → G in CAA64543 (PubMed:8688459).Curated1
Sequence conflicti928R → A in CAA64543 (PubMed:8688459).Curated1
Sequence conflicti936A → P in CAA64543 (PubMed:8688459).Curated1
Sequence conflicti1005A → D in CAA64543 (PubMed:8688459).Curated1
Sequence conflicti1185 – 1186SA → R in CAA64543 (PubMed:8688459).Curated2
Sequence conflicti1475 – 1476NG → TC in CAA64543 (PubMed:8688459).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X95255 mRNA Translation: CAA64543.1 Frameshift.
AC163610 Genomic DNA No translation available.
AC173115 Genomic DNA No translation available.
AC173210 Genomic DNA No translation available.
CCDSiCCDS36603.1
RefSeqiNP_032156.2, NM_008130.2
UniGeneiMm.5098

Genome annotation databases

EnsembliENSMUST00000110510; ENSMUSP00000106137; ENSMUSG00000021318
GeneIDi14634
KEGGimmu:14634
UCSCiuc007pns.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X95255 mRNA Translation: CAA64543.1 Frameshift.
AC163610 Genomic DNA No translation available.
AC173115 Genomic DNA No translation available.
AC173210 Genomic DNA No translation available.
CCDSiCCDS36603.1
RefSeqiNP_032156.2, NM_008130.2
UniGeneiMm.5098

3D structure databases

ProteinModelPortaliQ61602
SMRiQ61602
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199944, 6 interactors
ComplexPortaliCPX-151 GLI3-SUFU complex
CORUMiQ61602
STRINGi10090.ENSMUSP00000106137

PTM databases

iPTMnetiQ61602
PhosphoSitePlusiQ61602

Proteomic databases

MaxQBiQ61602
PaxDbiQ61602
PRIDEiQ61602

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000110510; ENSMUSP00000106137; ENSMUSG00000021318
GeneIDi14634
KEGGimmu:14634
UCSCiuc007pns.1 mouse

Organism-specific databases

CTDi2737
MGIiMGI:95729 Gli3

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00900000140802
HOGENOMiHOG000290688
HOVERGENiHBG005844
InParanoidiQ61602
KOiK06230
OMAiQYGNCLN
OrthoDBiEOG091G01XS
PhylomeDBiQ61602
TreeFamiTF350216

Enzyme and pathway databases

ReactomeiR-MMU-5610785 GLI3 is processed to GLI3R by the proteasome
R-MMU-5610787 Hedgehog 'off' state
R-MMU-5632684 Hedgehog 'on' state

Miscellaneous databases

PROiPR:Q61602
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021318 Expressed in 315 organ(s), highest expression level in urinary bladder
CleanExiMM_GLI3
ExpressionAtlasiQ61602 baseline and differential
GenevisibleiQ61602 MM

Family and domain databases

InterProiView protein in InterPro
IPR032851 GLI3
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PANTHERiPTHR19818:SF5 PTHR19818:SF5, 1 hit
PfamiView protein in Pfam
PF00096 zf-C2H2, 5 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 5 hits
SUPFAMiSSF57667 SSF57667, 3 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 4 hits
PS50157 ZINC_FINGER_C2H2_2, 5 hits
ProtoNetiSearch...

Entry informationi

Entry nameiGLI3_MOUSE
AccessioniPrimary (citable) accession number: Q61602
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 11, 2007
Last modified: November 7, 2018
This is version 165 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again